Triethylamine → HCID 86719482, compound

HRID 1772235Notes

Reaction equation

HRID 1772235 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]2[CH2:15][CH2:14][CH:13]([O:16][CH2:17][C:18]([OH:20])=O)[CH2:12][CH2:11]2)=[CH:5][C:4]=1[C:21]([F:24])([F:23])[F:22])#[N:2].[CH3:25]CN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[F:54][C:55]1[CH:56]=[CH:57][C:58]2[O:62][CH:61]([CH2:63][N:64]3[CH2:69][CH2:68][NH:67][CH2:66][CH2:65]3)[CH2:60][C:59]=2[CH:70]=1>ClCCl>[F:54][C:55]1[CH:56]=[CH:57][C:58]2[O:62][CH:61]([CH2:63][N:64]3[CH2:65][CH2:66][N:67]([CH2:25][C:18](=[O:20])[CH2:17][O:16][CH:13]4[CH2:12][CH2:11][CH:10]([NH:9][C:6]5[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:21]([F:23])([F:22])[F:24])[CH:5]=5)[CH2:15][CH2:14]4)[CH2:68][CH2:69]3)[CH2:60][C:59]=2[CH:70]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66365445HCID 66365445, compoundHCID 67283106HCID 67283106, compound

Product 1

HCID 86719482HCID 86719482, compoundYield 74.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-[(4-[[4-cyano-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]acetic acid (216 mg, 0.63 mmol, 1.5 eq) in dichloromethane (25 ml) was added EDAC.HCl (122 mg, 0.64 mmol, 1.5 eq), HOBt (86 mg, 0.64 mmol, 1.5 eq), triethylamine (128 mg, 1.26 mmol, 3 eq) and 1-[(5-fluoro-2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine (100 mg, 0.42 mmol) at room temperature. The solution was stirred at room temperature overnight, diluted with dichloromethane (150 ml), and washed with water (80 ml). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The crude material was purified by silica gel chromatography using 1-2% methanol in dichloromethane to elute. The product-containing fractions were combined and concentrated under vacuum to afford 4-[[4-(3-[4-[(5-fluoro-2,3-dihydro-1-benzofuran-2-yl)methyl]piperazin-1-yl]-2-oxopropoxy)cyclohexyl]amino]-2-(trifluoromethyl)benzonitrile as a white solid (0.18 g, 69%); (ES, m/z): [M+H]+ 561.20; 1H NMR (300 MHz, CDCl3): δ 7.56 (d, J=8.7 Hz, 1H), 6.81-6.92 (m, 3H), 6.64-6.71 (m, 2H), 5.13 (broad s, 1H), 4.29 (d, J=7.8 Hz, 1H), 4.21 (s, 2H), 3.67-3.77 (m, 3H), 3.34-3.47 (m, 3H), 2.92-2.99 (dd, J=˜8.1 Hz, ˜15.9 Hz, 1H), 2.51-2.89 (m, 5H), 2.15-2.25 (broadened d, J=9.9 Hz, 4H), 1.41-1.48 (m, 3H), 1.21-1.32 (m, 3H).

Workup

  1. washwashed with water (80 ml)
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe crude material was purified by silica gel chromatography
  6. washto elute
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-f6574f79f990481fb7ef67c47283ef67
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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